Does the Maternal Gut Microbiome Influence the Outcome of Perinatal Asphyxia?

This review explores the maternal gut microbiome's role in shaping neonatal neurodevelopmental outcomes following perinatal asphyxia (PA), a leading cause of infant mortality and disability with limited therapeutic options beyond hypothermia. We synthesized current evidence on microbiome-mediated neuroprotective mechanisms against hypoxic-ischemic brain injury. The maternal microbiome influences fetal development through bioactive metabolites (short-chain fatty acids, indole derivatives) that cross the placental barrier, bacterial antigen regulation, and infant microbiome colonization. These pathways activate multiple protective mechanisms: anti-inflammatory signaling via NF-κB suppression and regulatory T cell expansion; antioxidant defenses through Nrf2 activation; neural repair via BDNF upregulation and neurogenesis; and oxytocin system modulation. Animal models demonstrate that maternal dysbiosis from high-fat diet or antibiotics exacerbates PA-induced brain damage, increasing inflammatory markers and hippocampal injury. Conversely, probiotic supplementation, dietary fiber, and specific interventions (omega-3, resveratrol) reduce neuroinflammation and oxidative injury. Human studies link maternal dysbiosis-associated conditions (obesity, gestational diabetes) with adverse pregnancy outcomes, though direct clinical evidence for PA severity remains limited. Understanding the maternal microbiome-fetal brain axis opens therapeutic avenues, including prenatal probiotics, dietary modifications, and targeted metabolite supplementation to prevent or mitigate PA-related neurological sequelae, potentially complementing existing neuroprotective strategies.